Leukemia inhibitory factor regulates the activation of inflammatory signals in macrophages and trophoblast cells

Autor: Yassine Oufqir, Marion Ravelojaona, Julie Girouard, Carlos Reyes-Moreno, Céline Van Themsche, Cathy Vaillancourt, Christian Carrier, Angham Dallagi, Jovane Hamelin-Morrissette
Rok vydání: 2020
Předmět:
STAT3 Transcription Factor
0301 basic medicine
medicine.medical_treatment
Immunology
Gene Expression
Motility
Leukemia Inhibitory Factor
Cell Line
Interferon-gamma
03 medical and health sciences
0302 clinical medicine
Cell Movement
Pregnancy
medicine
Humans
STAT3
Maternal-Fetal Exchange
Molecular Biology
reproductive and urinary physiology
biology
Chemistry
Macrophages
Granulocyte-Macrophage Colony-Stimulating Factor
Trophoblast
Macrophage Activation
Coculture Techniques
Trophoblasts
Cell biology
STAT1 Transcription Factor
030104 developmental biology
Cytokine
medicine.anatomical_structure
Granulocyte macrophage colony-stimulating factor
Matrix Metalloproteinase 9
embryonic structures
biology.protein
Female
Tumor necrosis factor alpha
Inflammation Mediators
Cell activation
Leukemia inhibitory factor
Signal Transduction
030215 immunology
medicine.drug
Zdroj: Molecular Immunology. 120:32-42
ISSN: 0161-5890
DOI: 10.1016/j.molimm.2020.01.021
Popis: The pleiotropic cytokine leukemia inhibitory factor (LIF) is a key gestational factor known to establish dynamic cellular and molecular cross talk at the feto-maternal interface. Previously, we described the regulatory role of the LIF-trophoblast-IL10 axis in the process of macrophage deactivation in response to pro-inflammatory cytokines. However, the direct regulatory effects of LIF in macrophage and trophoblast cell function remains elusive. In this study, we aimed to examine whether and how LIF regulates the behavior of macrophages and trophoblast cells in response to pro-inflammatory stress factors. We found that LIF modulated the activating effects of interferon-gamma (IFNγ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in macrophages and trophoblast cells by reducing the phosphorylation levels of signal transducer and activator of transcription-1 (Stat1) and -5 (Stat5). Cell activation with IFNγ inhibited cell invasion and migration but this immobilizing effect was abrogated when macrophages and trophoblast cells were deactivated with LIF; macrophage cell motility restitution could in part be explained by the positive effects of LIF in Stat3 activation and matrix metalloproteinase 9 (MMP-9) expression. Pharmacological inhibition of Stat1 and Stat3 indicated that IFNγ-induced Stat1 activation mediated macrophage motility inhibition, and that cell motility in IFNγ-activated macrophages is restored via LIF-induced Stat3 activation and Stat1 inhibition. Moreover, IFNγ-induced TNFα gene expression was also abrogated by LIF through Stat1 inhibition and Stat3 activation. Finally, we have found that cell invasion of trophoblast cells is inhibited when they were cocultured with GM-CSF-differentiated, IFNγ-stimulated macrophages. This effect, however, was inhibited when macrophages were exposed to LIF. Overall, this in vitro study reveals for the first time the anti-inflammatory and pro-gestational activities of LIF by acting directly on macrophages and trophoblast cells.
Databáze: OpenAIRE
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